CLINICAL TOXICOLOGY, 22(1), 31-49 ( 1 9 8 4 )

TREATMENT OF ACUTE METHYLMERCURY INGESTION BY

H EMOD IAL YS IS WITH N-ACETY LCYSTE INE (MUCOMYST) INFUS ION AND
2,3-DIMERCAPTOPROPANE SULFONATE
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Mary Ellen Lund, M.D.

William Banner, Jr., M.D., Ph.D.*
Departments of Pediatrics and Pharmacology
University of Arizona
Tucson, Arizona 85724
Thomas W. Clarkson, Ph.D.
Department of Radiation Biology and Biophysics
Division o f Toxicology
University of Rochester
Rochester, New York 14642
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Maths Berlin, M.D.

Institute of Environmental Hygiene
University of Lund
Lund, Sweden

ABSTRACT
A case of acute methylmercury ingestion was treated
sequentially with oral D-penicillamine, hemodialysis during
N-acetyl cysteine (NAC) infusion, and 2,3-dimercaptopropane
sulfonate (DMPS) an experimental oral agent. Urinary organic
mercury elimination rate increased almost 40-fold during and
84-fold after hemodialysis with NAC infusion, compared with
elimination during initial D-penicillamine therapy. Mean
clearance during hemodialysis was only 13 ml/min with an

* For Reprints

31

Cowright 0 1984 by Marcel Dekker. Inc. 073 1-38 10/84/2201-O03 1$3.50/0

 32 LUND ET AL.

extraction rate of 3.7 mcg/min. Although whole blood mercury

concentrations decreased from 568 to 265 ng/ml during dialysis,
a rebound to 525 ng/ml occurred, A total of 1.6 mg mercury was
renally eliminated during hemodialysis and in the following 24
hours. A total of 3.3 mg of predominantly organic mercury was
renally eliminated during 18 days of combined therapies. Since
renal elimination of inorganic mercury is seen with chronic
methylmercury poisong, the high ratio of organic to inorganic
mercury in urine supports the acute nature of this exposure.
DMPS was begun on day 4 and during the two weeks o f
administration whole blood concentrations fell by 15% to 355
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ng/ml. An expected decrease in elimination half-life to 10

days was not observed during DMPS therapy, possibly due to
concurrent administration of vitamins containing zinc and
copper. The amount of methylmercury ingested was estimated as
45 mg, based on a post-distribution blood concentration of
approximately 450 ng/ml. The patient developed no symptoms o f
methylmercury poisoning during the one year after the episode.
We conclude that NAC may be useful to enhance renal elimination
of methylmercury and merits further investigation as a
potential binding agent to reduce the body burden of
.
met hy 1 mercury
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INTRODUCTION
Chronic methylmercury poisoning has heen investigated in
depth during outbreaks in Iraq and Minimata Bay, Japan (1,2).
To reduce the body burden of methylmercury in severely affected
individuals, several treatments were used during the Iraq
epidemic (3). All of these modal ities are based on the
affinity of methylmercury for sulfhydryl compounds.
The present case report is unique in two respects. First,
the patient presented within two hours of ingesting a single
dose of methylmercury, allowing us to follow the kinetics of a
single large dose. In addition, we used three treatments
serially, allowing us to compare the efficacy of oral
D-penicill amine, hemodialysi s with N-acetylcysteine (NAC)
infusion , and oral 2,3-dimercaptopropane sulfonate (DMPS).
 ACUTE METHYLMERCURY INGESTION 33

Case Report

A 20 year o l d male ingested 25 h a l o p e r i d o l t a b l e t s and 25

benztropine t a b l e t s along w i t h " 2 o r 3 l a r g e gulps" o f a
f u n g i c i d e c o n t a i n i n g 0.69% methylmercury i n an ethanol
c o n t a i n i n g base (Lawn Fungicide and I r o n , Germaine). About two
hours l a t e r , g a s t r i c lavage returned p i l l fragments and
p i n k - t i n g e d l i q u i d resembling t h e f u n g i c i d e , although t h e
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p a t i e n t reported t h a t he vomited a f t e r t h e ingestion.

A c t i v a t e d charcoal and magnesium c i t r a t e were i n s t i l l e d
f o l l o w i n g lavage. Toxicologic a n a l y s i s revealed t h e f o l l o w i n g :
h a l o p e r i d o l and benztropine i n u r i n e ; h a l o p e r i d o l and ethanol
i n g a s t r i c contents. Serum ethanol , methanol, isopropanol, and
acetone were nondetectable by g a s - l i q u i d chromatography.
A t t h a t time the methylmercury i n g e s t i o n was estimated a t
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800 mg and o r a l D-penicillamine, 500 mg every s i x hours, was

begun w i t h i n f o u r t o f i v e hours a f t e r t h e episode. Complete
blood count, serum e l e c t r o l y t e concentrations and
glutamic-aspartate aminotransferase (SGOT) l e v e l s were measured
on admission and were w i t h i n t h e normal range f o r each
determination.
Whole blood methylmercury concentration two hours a f t e r
i n g e s t i o n was 1930 ng/ml and 24 hours a f t e r i n g e s t i o n was 1007
ng/ml. On t h e basis o f these values (approximately 36 hours
a f t e r t h e i n g e s t i o n ) hemodialysis was begun w i t h NAC i n f u s e d
i n t o blood as i t entered t h e d i a l y z e r a t a r a t e t o produce 10
mM concentration. The f o l l o w i n g day (day 3 a f t e r i n g e s t i o n )
D-penicillamine was discontinued and o r a l DMPS was begun, 200
mg every s i x hours.
D e t a i l e d physical and neurologic examination was
completely normal on day 4 a f t e r t h e sedative e f f e c t s o f
h a l o p e r i d o l and benztropine had resolved. Visual f i e l d t e s t s ,
sensory and v e s t i b u l a r examination , and nerve conduction
v e l o c i t.ies were. normal.
 34 LUND ET AL.

On day 5 t h e p a t i e n t was t r a n s f e r r e d t o a p s y c h i a t r i c
h o s p i t a l where DMPS therapy was continued. A t the family's
request m u l t i v i t a m i n and mineral supplements from a h e a l t h food
s t o r e (GTC Vitamins, Bornson Pharmaceuticals) were s t a r t e d . At
the time of discharge from t h i s h o s p i t a l t h e p a t i e n t had
received a 14-day course o f DMPS. Because o f m i l d anorexia and
nausea, he e l e c t e d n o t t o continue t a k i n g DMPS as an
A t t h a t time t h e whole blood mercury was 355 ng/ml
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outpatient.
and the r e s u l t was e s s e n t i a l l y upchanged 48 hours l a t e r . Since
these concentrations were a t a l e v e l associated w i t h a low
r i s k o f chronic t o x i c i t y ( 2 , 4 ) , no f u r t h e r therapy was
recommended.
Serum z i n c and copper concentrations measured weekly
d u r i n g DMPS therapy remained normal and unchanged from
pre-therapy val ues.
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Neurological examination s i x weeks and one year a f t e r the

i n g e s t i o n was normal a1 though nerve conduction v e l o c i t i e s were
n o t repeated. The p a t i e n t denied and d i d n o t d i s p l a y a t a x i a ,
d y s a r t h r i a , v i s u a l f i e l d c o n s t r i c t i o n , and hearing loss.

MTERIAL AND METHODS

Mercury analysis

Whole blood and u r i n e samples were analyzed f o r t o t a l and

inorganic mercury content by atomic absorption spectroscopy
(5).
Q u a n t i t a t i o n o f methylmercury l e v e l s i n whole blood were
performed by gas chromatography ( 6 ) . Other blood o r serum
analyses were performed by t h e c l i n i c a l chemistry l a b o r a t o r y .
A sample o f the f u n g i c i d e ingested by t h e p a t i e n t was analyzed
and found t o be of 0.69% methylmercury.
 ACUTE METHYLMERCURY INGESTION 35

Hemodialysis w i t h N - a c e t y l c y s t e i n e i n f u s i o n

Informed consent was g i v e n by t h e p a t i e n t and h i s family.

A Centry 1067 hemodialyzer was used w i t h access o b t a i n e d v i a
the p a t i e n t ' s r i g h t subclavian vein. T h i s system r e q u i r e s o n l y
one access, a l t e r n a t i n g removal w i t h r e t u r n of blood. Blood
f l o w r a t e was m a i n t a i n e d a t a p p r o x i m a t e l y 125 ml/min t h r o u g h o u t
t h e 5.3 h o u r procedure, and d i a l y s a t e f l o w r a t e was 500 ml/min.
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S t e r i l e NAC f o r i n h a l a t i o n (Mucomyst, Mead Johnson

Pharmaceutical) was f i l t e r e d t o remove any p a r t i c l e s . A
Harvard pump was used t o i n f u s e NAC i n t o t h e l i n e c a r r y i n g
b l o o d i n t o t h e d i a l y z e r and t h e i n f u s i o n r a t e was a d j u s t e d t o
r e s u l t i n a 10 mM c o n c e n t r a t i o n c f NAC i n t h e b l o o d based on
t h e average b l o o d f l o w r a t e . Every 15 minutes, b l o o d samples
were removed f r o m stopcocks l o c a t e d a t t h e f o l l o w i n a s i t e s on
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t h e d i a l y z e r : e n t e r i n g t h e d i a l y z e r ( i n f l o w ) ; and a f t e r l e a v i n g
the dialyzer (outflow). A l l b l o o d was o f venous o r i g i n i n t h e
patient .
Cal c u l a t ions

I n i t i a l e s t i m a t e o f t h e dose o f methy1mercur.y i n g e s t e d was

based on h i s t o r y f r o m t h e p a t i e n t . A l o w e r , more a c c u r a t e
e s t i m a t e was made a f t e r t h e r e s u l t s o f s e r i a l whole b l o o d
mercury analyses were a v a i l a b l e . Based on d a t a f r o m v o l u n t e e r s
fed known amounts o f methylmercury, a t t h e end o f t h e
d i s t r i b u t i o n phase t h e b l o o d volume c o n t a i n s a p p r o x i m a t e l y f i v e
t o s i x p e r c e n t of t h e i n g e s t e d dose (7, 8 ) . Because
h e m o d i a l y s i s was performed a t a t i m e when t e r m i n a l e l i m i n a t i o n
would be expected t o begin, we used t h e mean o f v a l u e s f r o m
samples o b t a i n e d d u r i n g t h e 74 hours a f t e r h e m o d i a l y s i s . This
t i m e p e r i o d was chosen t o a d j u s t f o r t h e "rebound" v a l u e s
observed i n t h e 12 hours f o l l o w i n g t h e procedure.
 36 LUND ET AL.

Clearances were c a l c u l a t e d from t h e f o l l o w i n g standard

formulae:
E x t r a c t i o n Rate = Blood f l o w r a t e x (I- 0) where
Blood f l o w r a t e = 125 ml/min
I = Mercury concentration i n ng/ml o f blood e n t e r i n g t h e
d ia 1y ze r , 'I inf 1ow"
0 = Mercury concentration i n ng/ml o f blood l e a v i n g t h e
d ia 1yze r , "out f 1ow"
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Blood f l o w r a t e x (I- 0) - Extraction rate

Dialysance =
I I
R e l a t i v e e x t r a c t i o n o f mercury i s t h e per cent o f mercury
-
e x t r a c t e d from p a i r e d i n f l o w and o u t f l o w samples , I O x 100.
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-
DMPS
2,3-dimercaptopropane sulfonate, DMPS (Heyl Pharmaceutical
Company, West B e r l i n ) , was a g i f t o f Heyl Pharmaceutical
Company. An I n v e s t i g a t i o n a l New Drug permit. was obtained from
the Food and Drug A d m i n i s t r a t i o n p r i o r t o beginning therapy and
the i n v e s t i g a t i o n a l n a t u r e o f t h e drug was explained t o t h e
p a t i e n t and h i s family, both o f whom gave informed consent.

RESULTS

Est imat ion o f met hy 1mercu r y dos e

Since f i v e t o s i x per cent o f t h e dose d i s t r i b u t e s i n t o

the blood volume and t h e mean concentration o f t h e e i g h t values
measured i n t h e 24 hours a f t e r d i a l y s i s was 450 ng/ml, we
estimate t h a t our p a t i e n t absorbed approximately 45 mg o f
met hy 1mercury .
 ACUTE METHYLMERCURY I N G E S T I O N 37
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I I 1 1
0 2 4 6 0 10
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Figure 1: Whole blood mercury concentrations a r e shown f o r t h e

e n t i r e study period. Following an i n i t i a l sharp increase, t h e
semi-logarithmic p l o t shows a biexponential d e c l i n e d u r i n g
which various i n t e r v e n t i o n s occurred. The d i a l y s i s p e r i o d i s
shown (*). The rebound i n concentration a f t e r d i a l y s i s
probably represents r e d i s t r i b u t i o n o f mercury from t i s s u e s i n t o
blood

Whole blood mercury concentrations

The whole blood mercury concentration was 2800 ng/ml two

hours a f t e r the ingestion. Rapid d e c l i n e o f mercury
concentration o f whole blood d u r i n g t h e f i r s t 12 hours probably
represents t h e d i s t r i b u t i o n phase. Hemodialysis w i t h NAC
i n f u s i o n reduced t h e whole blood concentration f u r t h e r , b u t i n
the 12 hours f o l l o w i n g t h e procedure, l e v e l s g r a d u a l l y rose
("rebound") although they d i d n o t reach p r e - d i a l y s i s values of
almost 500 ng/ml ( F i g u r e 1). The mean o f t h e e i g h t values
observed d u r i n g t h e 24 hour p e r i o d a f t e r d i a l y s i s was 450
 38 LUND ET AL.

ng/ml, which we designate as t h e concentration a t t h e s t a r t o f

the terminal e l i m i n a t i o n phase. Following t h e 4 t h day a f t e r
ingestion, concentrations f l u c t u a t e d b u t showed a very gradual
decl ine.

E f f e c t o f treatments on whole blood concentrations

Because o f v a r i a b i l i t y i n r e s u l t s we were unable t o

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determine t h e e l i m i n a t i o n h a l f - 1 i f e d u r i n g each o f t h e
treatments. Decline o f concentrations d u r i n g o r a l
D-penicillamine therapy on days 1 and 2 may be a t t r i b u t a b l e t o
t i s s u e d i s t r i b u t i o n o f methylmercury. There was no appreciable
decrease i n concentrations d u r i n g D-penicil lamine
a d m i n i s t r a t i o n a f t e r hemodialysis; i n f a c t , concentrations
rose.
During hemodialysis, concentrations decreased by
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approximately 50%. These lower concentrations were t r a n s i e n t ,

as seen i n Figure 1. The mean r e l a t i v e e x t r a c t i o n d u r i n g t h e
procedure was 1.03%, ranging from 0 ( i n two sample p a i r s
obtained a t the end o f d i a l y s i s ) t o 22% (near t h e s t a r t o f
d i a l y s i s ) (Figure 2 ) . I f t h e l a s t two p a i r s o f samples are
omitted from c a l c u l a t i o n s on t h e b a s i s t h a t they may have been
improperly l a b e l l e d , then t h e mean r e l a t i v e e x t r a c t i o n would be
12.9%.
Mean dialysance o f mercury was 13.0 ml/min (range o f 0 t o
27.6) w i t h a mean e x t r a c t i o n r a t e of 3.7 rncg/min (range of 0 t o
8.9). Again, no dialysance o r e x t r a c t i o n occurred i n the l a s t
two p a i r s of samples. O m i t t i n g these two p a i r s from
c a l c u l a t i o n s , mean dialysance would be 16.2 ml/min w i t h 4.6
mcg/min mercury extracted. T o t a l amount o f mercury e x t r a c t e d
during the procedure was 1.11 mg, o r about 2% o f t h e 45 mg
estimated absorbed,
Oral DMPS therapy begun on the f o u r t h day a f t e r i n g e s t i o n
 ACUTE METHYLMERCURY INGESTION 39

3
0:
"0001
J

iYl
; :
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-1
6
P
n
0
%.- - * - d
8
W
Legend
-I b ARTERIAL
8 0 LENCUS-
100-1 1 I 1 1 1
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Figure 2: Mercury concentrations are shown as f u n c t i o n o f time

during d i a l y s i s and NAC i n f u s i o n . Blood samples e n t e r i n g t h e
dialysis coil (u) and e x i t i n g t h e c o i l (0--4))
are shown.

d i d n o t appear t o have an appreciable e f f e c t on whole blood

mercur.y concentrations (Figure 3). During t h e 14 day course o f
therapy concentrations declined by 15%, from 418 t o 355 ng/ml.
Because o f t h e v a r i a b i l i t y o f t h e data p o i n t s , we were unable
t o a c c u r a t e l y determine e l i m n a t i o n ha1f -1 f e y b u t i n s p e c t i o n
o f t h e r e s u l t s suggests t h a t t h e ha1f - 1 i f e exceeds ( t h e
expected) 10 days ( 3 ) .

U r i n a r y e x c r e t i o n o f organic mercury

Results a r e summarized i n t h e Table. D-penicillamine

administered when whole blood mercury concentrations were
maximal , produced l i t t l e u r i n a r y mercury e x c r e t i o n i n t h e 42
 40 LUND ET AL.
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1004 I 1 1 I 1
0 10 20 30 40 50
DAYS FROM INGESTION
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Figure 3: Mercury concentrations d u r i n g ( U and )

following o(- -4) DMPS therapy. Whole blood samples for
mercury analysis were obtained a t approximately the same time
each day.

hours following the ingestion. Urinary mercury excretion rate

increased 40-fold from 0.9 t o 44.0 ug/hr during hemodialysis
w i t h NAC infusion, and 84-fold from 0.9 t o 84.3 u g / h r i n the
16.5 hours a f t e r dialysis, DMPS was more effective t h a n
D-penicil lamine for enhancing urinary mercury e l imination.
During the 18 days of therapy, 3.3 mg of mercury was recovered
in the urine. I n the f i r s t three days of therapy, especially
during and immediately a f t e r NAC infusion, Greater t h a n 90% of
urinary mercury was i n the organic form (methylmercury). In
the 14 days t h a t followed, the percent o f organic methylmercury
eliminated i n urine was never less t h a n 75%.
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Table 1 - Urinary Organic Mercury Elimination

Day After Hours of Mercury Excretion Rate % Organic
Treatment Ingestion* Col 1e c t i on Excreted (mg) (lJg/hr) Mercury
D-Penicillamine 1-2 42 0.38 0.9 91%
(500 mg q 6 h r s )
Hemodialysis w i t h NAC i n f u s i o n 2 5.3 .235 44.0 96%
D-Penicillamine following NAC 3 16.5 1.391 84.3 97%
Dimercaptopropane Sul f o n a t e 4-6 68 .443 6.5 90%
(200 mg q 6 hrs)
Dimercaptopropane S u l f o n a t e 7 24 .129 5.3 84%
(200 mg q 6 h r s )
Dimercaptopropane Sul f o n a t e 8 24 .lo4 4.3 89%
(200 mg q 6 h r s )
Dimercaptopropane Sul f o n a t e 9 24 .082 3.4 83%
(200 mg q 6 h r s )
D i me r c a p t o p r o pa n e Su 1f on a t e 10-18 Sum of d a i l y .985 5.1 75%
(200 mg q 6 hrs) collections
TOTAL 3.295
*Day o f i n g e s t i o n counted a s day 1
 42 LUND ET AL.

DISCUSS ION
Vethylmercury i s completely and rapidly absorbed from the
intestine and i s distributed within four t o 14 hours i n t o body
tissues, particularly the b r a i n ( 9 ) . Because toxic effects may be
irreversible once they appear, most workers agree t h a t treatment
prior t o tissue accumulation and onset o f symptoms may prevent
permanent central nervous system damage. Experimental evidence in
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r a t s supports t h i s idea (10, 11).

Unfortunately methylmercury poisoning i n man is usually
accidental and unrecognized until 4 t o 6 weeks a f t e r neurologic
symptoms appear: paresthesias, dysarthria, a t a x i a , visual f i e l d
impairment, etc. Thus treatment t o reduce the body burden i s
generally begun long a f t e r methylmercury has distributed into the
brain. In this case the i n i t i a l concentration of methyl mercury
(1930 ng/ml) was i n a concentration range associated w i t h a 60%
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incidence o f neurologic deficity (12) i n chronic ingestions.

The case described here i s unique because the patient came

t o medical attention a f t e r an acute, single ingestion, and
because there were no available data t o assess the likelihood
or severity of potential methylmercury toxicity. Thus, we were
able t o document the course of a large, a l b e i t unknown, dose of
methylmercury and intervene before the onset of symptoms.
Another unique aspect o f t h i s case is the h i g h r a t i o
(greater t h a n three t o one) of organic t o inorganic mercury.
In chronic exposures t o methylmercury, less than 30% of urinary
mercury was organic (1). Our f i n d i n g t h a t greater t h a n 75% of
urinary mercury was i n the organic form has n o t been observed
in man. However, animal data agree w i t h our obsevation t h a t
following acute exposure to methylmercury, renal ly excreted
mercury i s primarily i n the organic form (13). From a
diagnostic s t a n d p o i n t , a h i g h per cent of urinary organic
mercury i s suggestive of acute exposure.
 ACUTE METHYLMERCURY INGESTION 43

Various sulfhydryl -containing binding agents have been

evaluated in animals and man. D-penicillamine was one of the
earliest agents found to enhance urinary elimination of
methylmercury (14). Since methylmercury undergoes extensive
enterohepatic recirculation (13), non-absorbable agents have
been used to "trap" methylmercury excreted into bile. A
polystyrene resin containing fixed sulfhydryl groups reportedly
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enhanced overall methylmercury elimination by 50% (15), and

when it was administered to poisoned humans, this resin
decreased the average elimination half-life from 65 to 20 days
(3). This material was not available for use in this patient.
Similarly in an --
in vitro model using methlymercury containing
human plasma, agarose encapsulated or polymercaptal
nicrospheres rapidly cleared up to 40% o f the mercury (16).
Other binding agents including L-cysteine,
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N-acetyl-penicillamine, and NAC have been studied for possible

use during hemodialysis and show a concentration-dependent
enhancement of methylmercury dialysance --in vi tro (17). The
optimal concentration o f these agents under experimental
conditions was 10 mM. In the dog about 10% of a methylmercury
dose can be hemodialyzed when this concentration of L-cysteine
is infused into arterial blood entering the dialyzer, compared
with negligible clearance without cysteine. However relative
extraction depends on blood and dialysate flow rates and the
rate of methylmercury diffusion between blood and dialysate, as
well a s cysteine concentration in the blood (18). A similar
system later used in several patients with severe methylmercury
poisoning successfully extracted almost 50% of the whole blood
mercury (19). These patients had a1 ready sustained permanent
neurologic damage, so the efficxy of the procedure was
difficult tc! assess. However, decreasing the body burden of
methylmercury may have prevented progression o f damage and
 44 LUND ET AL.

possibly led to some improvement in one patient.

Unexpectedly we found that hemodialysis with infusion of
NAC did not remove more than two t o four per cent of the
estimted amount ingested, despite the fact that the procedure
was performed when blood concentrations were very high. The
differences between inflow and outflow blood concentrations
during dialysis represented an average relative extraction df
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only one per cent. This value is considerably less than the
48% relative extraction reported by Al-Abbasi et al, when 10 mM
L-cysteine was infused into the arterial line of a hemodialyzer
(19). There are distinctions between the two cases. In
addition to using a different binding agent, they used a slower
blood flow rate, 40 ml/min, and whole blood mercury
concentration at the start of dialysis was 50 ng/ml in their
patient. Furthermore, the dialyzer utilized in the earlier
For personal use only.

report had separate arterial and venous blood sources, whereas

the Centry 1067 withdraws and returns blood from a single site;
in this case, the right subclavian vein. Although we
calculated a rate o f infusion to produce 10 mM NAC in blood
entering the dialyzer, we could not determine actual NAC
concentrations in the blood. Any or several of these
differences may explain the ineffectiveness o f hemodialysis in
our patient,
To our surprise, there was a striking increase in urinary
excretion of methylmercury during and following hemodialysis
with NAC infusion. This increase was 44- and 84-fold,
respectively, relative to excretion during D-penicillamine
administration. Since the D-penicillamine given prior to
dialysis (when whole blood mercury concentrations were highest)
resulted in little urinary organic mercury, some other factor
probably was responsible for the large increase of urinary
mercury during dialysis and in the 16.5 hours afterward. We
 ACUTE METHYLMERCURY I N G E S T I O N 45

f e e l t h a t NAC may have enhanced renal e x c r e t i o n i n e i t h e r o r

both o f the f o l l o w i n g ways. N-acetylcysteine-methylmercury
complexes may n o t have been completely cleared as blood passed
t h e d i a l y s i s c o i l , and these water soluble complexes then were
f i l t e r e d v i a t h e kidney. S i m i l a r l y , undialyzed NAC may have
been a v a i l a b l e t o b i n d methylmercury and form a
renal l y - e x c r e t a b l e complex. A1 though these explanations a r e
hypothetical , preliminary animal data supports our f i n d i n g t h a t
Clinical Toxicology Downloaded from informahealthcare.com by University of Adelaide on 05/28/14

NAC enhances renal e l i m i n a t i o n o f methylmercury (personal data

o f T.W. Clarkson).
N-acetylcysteine may be u s e f u l f o r t r e a t i n o methylmercury
intoxication. Whether i t would be o f b e n e f i t i n cases o f
chronic poisoning deserves study. The ease o f o r a l NAC
a d m i n i s t r a t i o n makes i t p r e f e r a b l e and l e s s expensive than
hemodialysis w i t h a b i n d i n g agent. I.Je would have administered
For personal use only.

o r a l NAC a f t e r t h e hemodialysis had we known t h e r e s u l t s o f

u r i n a r y mercury samples e a r l i e r i n our p a t i e n t ' s course.
Data from t h i s acute i n g e s t i o n sugaests t h a t NAC may be
more e f f e c t i v e than e i t h e r D-penicillamine o r DMPS f o r
enhancing u r i n a r y organic mercury e l i m i n a t i o n . During DMPS
therapy u r i n a r y organic mercury e x c r e t i o n was l e s s than
expected from studies i n animals (20, 21). Clarkson e t a l .
( 3 ) reported a decrease i n average e l i m i n a t i o n h a l f - l i f e from
6 1 t o 10 days w i t h o r a l DMPS treatment, a f i n d i n g we d i d n o t
observe. As shown i n Figure 3, t h e f l u c t u a t i o n o f whole blood
mercury concentrations d u r i n g DMPS therapy and t h e re1 a t i v e
s h o r t d u r a t i o n o f therapy precluded c a l c u l a t i o n o f a value f o r
e l imination half-1 i f e .
What might e r p l a i n the seemingly poor performance o f DMPS
i n the present case? P a t i e n t noncompliance w i t h therapy i s
possible b u t u n l i k e l y . During t h e two weeks he received DMPS,
t h e p a t i e n t was h o s p i t a l i z e d and observed by s t a f f personnel t o
take the medication. I n a d d i t i o n , the p a t i e n t s t a t e d a
 46 LUND ET AL.

willingness to comply with therapy intended to reduce his blood

mercury concentrations. Since evidence in rats indicates that
DMPS is excreted unchanged in the urine ( 2 2 ) , individual
metahol ic differences should not affect the results of therapy.
A possible explanation of the less-than-expected urinary
excretion of organic mercury during DMPS therapy is the
concurrent administration of vitamins cont.aining copper
gluconate 0.29 and zinc oxide 5.0 mg (along with numerous fat
Clinical Toxicology Downloaded from informahealthcare.com by University of Adelaide on 05/28/14

and water soluble vitamins). In a recent review, Aposhian

notes that DMPS is reportedly useful for reducing serum copper
concentrations of patients with Wilson's disease and that it
binds to other heavy metals such as zinc ( 2 3 ) . Since our
patient received his vitamins and DMPS at about the same time
each day, the DMPS may have bound to copper and zinc in the
stomach and intestinal lumen, resulting in less agent available
For personal use only.

to bind with methylmercury. Despite lacking ev dence for this

theory, we noted that during the course of DMPS the patient's
plasma zinc and copper concentrations remained n pre-therapy
normal ranges, instead of decreasing, an observation made by
others (unpublished data from T.W. Clarkson). Thus, we do not
feel that our experience with DMPS is strong evidence against
its usefulness as a binding agent for methylmercury poisoning.
We feel that our observation of enhanced urinary
elimination of organic mercury during and following NAC
administration deserves investigation in animals for
verification and elucidation of its mechanism of action. Since
this agent is readily availahle in the United States,
substantiation of greater efficacy than D-penicillamine and
DMPS would facilitate treatment of both acute and chronie
.
met hy 1 mercury po i soni ng
 ACUTE METHYLMERCURY INGESTION 47

ACKNOWLEDGEMENTS

D r . Lund was a f e l l o w i n c l i n i c a l pharmacology supported b y

USPHS t r a i n i n g g r a n t # GMO7533-05. Her c u r r e n t address i s Centers
For Disease C o n t r o l , B i r t h D e f e c t s Brnach, 1600 C l i f t o n Road,
At1 anta , Georgia 30333.
The a n a l y t i c a l c a r e group o f t h e Environmental H e a l t h Sciences
Clinical Toxicology Downloaded from informahealthcare.com by University of Adelaide on 05/28/14

Center a t Rochester, New York and Vrs. E l l e n F. M i l e s s p e n t l o n g

hours i n t h e l a b o r a t o r y p e r f o r m i n g t h e mercury a n a l y s i s .
Supported i n p a r t by a c e n t e r g r a n t f r o m N a t i o n a l I n s t i t u t e s
o f Environmental H e a l t h Sciences (FSO1247) and by a g r a n t from
N a t i o n a l I n s t i t u t e s o f H e a l t h (GM25329).
G a i l Herod p r o v i d e d i n v a l u a b l e t e c h n i c a l a s s i s t a n c e .

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 ACUTE METHYLMERCURY INGESTION 49

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